The main objective of this project is to determine if there is an interaction between agents which cause alterations in drug metabolism and the potential of inhaled chlorinated hydrocarbons to produce either spontaneous or epinephrine-induced arrhythmias. Rabbits pretreated with inhibitors of microsomal drug metabolism (e.g., SKF525A) and exposed to trichloroethylene tend to develop arrhythmias in a shorter period of time than do controls. Inducing agents such as phenobarbital tend to protect. Ethanol, pyrazole and caffeine administration decreased metabolism and increased arrhythmias whereas amphetamine elevated trichloroethylene blood levels without increasing arrhythmias, and disulfiram while inhibiting metabolism protected against arrhythmia production. Similar studies on the relationship between the metabolism of chlorinated compounds and their arrhythmigenic potential are being conducted with halothane, chloroform, methylchloroform and tetrachloroethylene.